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REVIEW ARTICLE
Year : 2017  |  Volume : 15  |  Issue : 4  |  Page : 295-301

Inheritance patterns of localized aggressive periodontitis: A systematic review


1 Department of Public Health Dentistry, KVG Dental College and Hospital, Sullia, India
2 Department of Dentistry, Mysore Medical College and Research Institute, Mysore, Karnataka, India

Date of Web Publication13-Dec-2017

Correspondence Address:
Dr. Jaseela Praveena
Department of Public Health Dentistry, KVG Dental College and Hospital, Sullia - 574 327, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaphd.jiaphd_73_17

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  Abstract 

Inheritance patterns are traits/diseases that are passed from parents to offspring through genes. Elucidation of inheritance pattern of localized aggressive periodontitis may permit us to have a better understanding of the disease etiology, thereby allowing improved classification, diagnosis, and treatment of this aggressive type of periodontal disease. This review aims to determine the pattern of inheritance of localized aggressive periodontitis through critical evaluation of literature and to evaluate various genetic analyses for determining the mode of inheritance. Records were searched from various databases such as PubMed/Medline, Cochrane, and EMBASE. Articles published over the past 40 years (1972–2012) were identified using the key search terms. A total of 121 records were identified by title/abstracts and were retrieved. Potentially relevant reports identified from the reference lists of review articles and chapters were also hand searched. Eighteen articles met the inclusion criteria, and these studies were assessed independently for the methodology and performance. Each study was scored according to STREGA guidelines. Out of the various patterns of inheritance reported in literature, 38.9% of the studies supported an autosomal recessive mode of inheritance, whereas 27.7% showed X-Linked dominant pattern, 16.67% reported autosomal dominant inheritance, 11.11% reported a recessive mode of inheritance, and 5.56% showed dominant mode of inheritance. Thus it can be concluded that even though the inheritance pattern apparently shows an autosomal recessive mode of inheritance, the data are meager to conclude that localized aggressive periodontitis is solely inherited through autosomal recessive mode as there are various other factors playing a hand in the occurrence of the disease. Hence, it would not be erroneous to say it is multifactorial or may be largely inconclusive.

Keywords: Genetics, juvenile periodontitis, localized aggressive periodontitis


How to cite this article:
Praveena J, Battur H, Fareed N, Khanagar S, Bhat M. Inheritance patterns of localized aggressive periodontitis: A systematic review. J Indian Assoc Public Health Dent 2017;15:295-301

How to cite this URL:
Praveena J, Battur H, Fareed N, Khanagar S, Bhat M. Inheritance patterns of localized aggressive periodontitis: A systematic review. J Indian Assoc Public Health Dent [serial online] 2017 [cited 2024 Mar 29];15:295-301. Available from: https://journals.lww.com/aphd/pages/default.aspx/text.asp?2017/15/4/295/220719


  Introduction Top


Inheritance patterns are traits/diseases that are passed from parents to offspring through genes. Gregor Mendel, an Austrian monk, in the second half of the 19th century was the pioneer in the studies of inheritance patterns.[1] Observing the identifiable traits/characteristics (phenotypes) passed on from generation to generation is the oldest form of genetics studies. Of late, many a genetic models and analysis that pinpoint disease genes/specific chromosomes is available, still tracing inheritance patterns through phenotypes remains as a fundamental step because unless phenotypes are accurately described in a way that is biologically sensible genetic models will be flawed. Studies of inheritance patterns of serious disorders such as hemophilia, thalassemia, and sickle cell anemia help in mapping or tracking disease transmission through generations, enabling prevention through informed decisions improving the quality of life, and helping to cope with the disease.[2],[3],[4]

Elucidation of inheritance pattern of localized aggressive periodontitis (LAP) may permit us to have a better understanding of the disease etiology, thereby allowing improved classification, diagnosis, and treatment of this aggressive type of periodontal disease. LAP is a form of periodontal disease which is characterized by severe rapid progressive periodontal destruction, in which the amount of microbial deposits is inconsistent with the severity of destruction indicating a genetically determined susceptibility of the host. The age group of affected patients is typically 12–26 years of age, with a sex ratio showing a female predilection.[5]

Earlier stages of the disease process are characterized by interproximal attachment loss on at least two permanent teeth, one of which is the first molar, and involving no more than two teeth other than first molars and incisors.[6] As the disease progresses development of distolabial migration of incisors with diastema formation, mobility of the involved teeth, sensitivity of the denuded root, deep dull radiating pain to the jaw, periodontal abscess, and lymph node enlargement may occur.[5]

The exaggerated occurrence of LAP within families is indicative of the genetic predisposition of this disease. Various studies have reported disproportionately high prevalence of LAP among twins, parents and offsprings, siblings, first cousins, uncles, and nephews from certain families, with >40%–50% of members affected.[7] Even though microbial and other environmental factors initiate and modulate periodontal diseases, individuals are known to respond differently to them due to their individual genetic profile.[8] Hence, family studies were conducted and still remains the best approach for genetic studies of LAP.

The prevalence of LAP varies among different races and ethnic groups suggesting genetic variations with ethnicity. The global prevalence of LAP is reported to be below 1%.[9],[10] The prevalence of the disease among African population and those of African descendants are 1%–5%, prevalence rates are estimated to be 2.6% among African-Americans, 0.5%–1.0% among Hispanics in North America, and 0.3%–2.0% among South Americans and Caucasians.[11],[12] The disease prevalence is reported to be 0.1% in Northern and in Central Europe, 0.5% in Southern Europe, and 0.1%–0.2% in North America.[12],[13] In Asia, the prevalence rate is 0.2%–1.0%, 1.2% in Baghdad and Iran, 0.42% in Saudi Arabia, and 0.47 in Japanese population.[12],[13] The prevalence of LAP in India varies widely ranging from 0.36% in Mangalore and 1.5% in Moradabad to 6.80% in Mumbai.[14],[15]

The initial studies conducted on individual families reported different modes of inheritance. Autosomal recessive mode of inheritance was reported by Fourel 1972 and Jorgenson et al. 1975, whereas Melnick et al. 1976 reported X-linked dominant mode of inheritance. Since then, various studies have been conducted on small and large single/multiple families giving varying results and divergent modes of inheritance.[16],[17],[18]

LAP presents an interesting range of problems for genetic analysis due to varying age of onset, low prevalence rate, sex-specific incidence, difficulty in obtaining accurate clinical histories on edentulous patients to establish cause of tooth loss, difficulty involved in obtaining multigenerational data, and adequate sample size. This systematic review is thus undertaken to critically analyze literature on inheritance of LAP with an aim to determine the pattern of inheritance of localized aggressive periodontitis through critical evaluation of literature.


  Materials and Methods Top


This systematic review was carried out based on Joanna Briggs Institute (JBI) guidelines.[19] Literature identification and selection were performed through core databases such as (PubMed, MEDLINE, EMBASE, Cochrane, and Google scholar using a combination of at least two keywords such as Genetic basis/inheritance pattern/heredity of Juvenile periodontitis/LAP/Early-onset periodontitis, periodontosis etc.) and abstracts/full-length articles were retrieved by JP, qualitative synthesis of data was performed by HB, NF, and SK.

The manuscript selection was conducted at two stages. First, a decision was made based on the title and abstracts pertaining to the research topic. The preliminary search yielded 121 abstracts which suited our aim. (EBSCOhost yielded around 3 records, PubMed search resulted in 52 records, ScienceDirect provided 3 records, and 43 records were obtained from Google Scholar, Wiley online library generated 11 records, and Lippincott Williams provided 3 records. Searching other nonelectronic sources such as hand searching of journals; dissertations of other universities provided an additional 6 records).

A total of 37 articles were eliminated due to duplication, 84 full-length articles were thus retrieved at the second stage and critically assessed for inclusion by the team consisting of the first three authors. A total of 58 articles were excluded at the second level, as they were either not related to the main outcome of our study and/were linkage analyses which associated LAP to specific gene locus but did not point toward the mode of inheritance.

Finally, 27 full-length manuscripts including a translated version of a non-English manuscript (Chinese) were circulated among all members of the review team. To eliminate bias, blinding of the manuscripts was performed by blocking the name of journal and that of the authors by chief investigator herself before circulating it among the team, who then decided on whether the article should be included in the review or not. Based on the interpretations of the team, 9 articles were excluded due to disagreement among the team members. Those records with unanimous acceptance were included, mutual discussions enabled inclusion/exclusion. Thus, a total of 18 articles were finally included in this systematic review, as shown in [Figure 1].
Figure 1: Diagram of the systematic review and searches for inheritance pattern of localized aggressive periodontitis

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These 18 articles were critically assessed by all the authors based on the STREGA STrengthening the REporting of Genetic Association Studies) guidelines containing a 22-item checklist.[20] The level of evidence was determined according to the JBI levels of evidence as shown in [Table 3].


  Results Top


A total of 18 studies conducted over 40 years were included in this systematic review. The analysis of literature revealed that 2–5 generations of families of 294 probands (78% of females) have been studied. Three types of genetic analyses have been employed to understand the inheritance patterns.

Analysis of the literature in relation to different time zones revealed that autosomal recessive mode of inheritance to be the more commonly reported mode of inheritance in the 70s and 80s, whereas from 1990 onward both autosomal recessive and autosomal dominant patterns have been equally reported. Our analysis of literature revealed differences in reporting of inheritance patterns in relation to age, number and gender of proband, generations of family studied, and types of analysis employed in various studies [Table 1].
Table 1: Analysis of literature based on the patterns of inheritance

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Autosomal recessive mode of inheritance was predominantly reported at 38.9%. Other forms of inheritance were X-Linked dominant pattern (27.7%), autosomal dominant inheritance (16.67%), reported a recessive mode of inheritance (11.11%) and dominant mode of inheritance (5.56%) [Table 2].
Table 2: Inheritance patterns of localized aggressive periodontitis as reported in literature

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Studies were analyzed for levels of evidence according to JBI. Out of 18 studies, 14 studies (77.77%) had evidence level of 4-B and four studies (22.22%) had evidence level of 4-C [Table 3].
Table 3: Quality of evidence

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Analyses revealed that majority of the studies were conducted in the USA (11 studies). Other studies were conducted in Finland (2 studies), UK (1 study), France (1 study), Egypt (1 study), Israel (1 study), and China (1 study). All major racial population such as Caucasians (11 studies), Mongoloids (1 study), and Negroid (6 studies) races have been the studied [Table 4].
Table 4: Overall analysis of literature of included studies in this review[13],[14],[15],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32]

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  Discussion Top


Inheritance pattern of a disease gives an insight into the etiopathogenesis of the disease. It enables us in the identification of possible risk factors associated with the disease. Timely intervention and management of these genetic diseases by diagnosis, counseling, and treatment will help the individual and the family in understanding their risks and options and to empower them to make informed decisions to seek early care. While the inheritance patterns of major genetic disorders that are more morbid and cause serious debilitation to the person affected and devastation to the families are well documented, the inheritance pattern of LAP still remains very inconsistent and unclear.[2],[3],[4]

Studies conducted to determine the pattern of inheritance reports wide variance. Sussman and Baer reported a case of juvenile periodontitis affecting a family over three generations (17-year-old girl, her 30-year-old mother, and 50-year-old grandmother) claimed that juvenile periodontitis (LAP) had X-linked dominant mode of inheritance.[36] Fourel and Jorgenson et al. reported autosomal recessive mode of inheritance and illustrated the possibility of periodontitis then known as periodontosis/periodontal syndrome to be a hereditary disease transmitted by a recessive gene by pedigree analysis of a series of 6 cases.[16],[17] Long et al. reported an autosomal recessive inheritance in a comprehensive study of 33 families which included two-, three-, and four-generation families.[29]

The credibility of results from a single study is questionable due to a relatively limited sample size and varying number of generations in the studies. Systematic reviews and qualitative synthesis of multiple studies are presently being used to overcome such limitations and to have a better understanding of the research question. There are no similar systematic reviews reported in the literature. The present systematic review, based on 18 studies, is thus aimed to provide a comprehensive analysis to map the inheritance pattern/genetic mode of inheritance of LAP. Our results indicated that majority of the studies showed autosomal recessive inheritance. These results are consistent with those of the largest sample and multiple generation study, including a total of 73 probands and four generations,[35] but in contrast with the results of the linkage analysis done over five generations of a family with 70 members which supported an autosomal dominant inheritance pattern.[26]

Analysis showed a paradigm shift from 1972 to 2012 in the genetic analysis from pedigree to segregational with proband age >20 showing majority of autosomal recessive inheritance while age <20 demonstrated X-linked dominant mode of inheritance. Further evaluation revealed while studies with single probands gave inconsistent results, multiple probands (>20) showed about 85.75% autosomal recessive inheritance.

In earlier studies, increased prevalence of females was attributed to X-linked dominant trait but later on female preponderance was related to selection bias or the simple fact that females are more concerned about their oral health, hence approached more for consultation.[37] The study participants ascertained by male proband showed equal results for autosomal recessive and X-linked dominant, whereas the studies with female probands or predominantly female proband showed autosomal recessive inheritance and about 78% of the studies had predominantly female probands.

There are lot of factors that lead to the conclusion of a particular mode of inheritance, and each such factor is at risk of bias such as the proband age, gender, origin, environment, generations studied and/or the genetic analysis used. The results obtained in our analysis were not sufficient enough to pinpoint LAP to have a definite inheritance pattern, indicating role of ethnic background and/or environment. Hence, it would not be wrong to assume that LAP is a multifactorial disease such as diabetes with a poorly defined inheritance pattern, and the scarce number of studies is probably due to the fact that LAP is considered as not so serious/debilitating as other genetic disorders which affects the quality of life of the patient and their kin.

In our analysis, all manuscripts were critically appraised using the STREGA guidelines containing 22 items.[20] Evidence level was calculated using JBI criteria.[19] Most of the articles had an evidence level of 4-B, four articles had an evidence level of 4-C which can be considered as limited evidence. The type of studies included also posed a major problem, due to minimum available studies on the participant case reports, case series, and observational studies were included leading to decreased evidence level.

Major limitation of this systematic review is the limited literature available on the subject studied. Even though attempts were made to collect relevant studies with minimum bias, publication bias, negative results not being reported, and language restrictions are limitations to this study. Due to the incomplete data on origin in the included studies, we were unable to assess the role of ethnicity on LAP susceptibility.

Family linkage studies are the most appropriate means of confirmation of proposed mode of inheritance and risk gene identification; hence, more studies should be undertaken in this aspect. New system should be developed for the diagnosis of relatives of LAP probands retrospectively. Relatives of the proband who were unavailable for a full periodontal examination, were edentulous, or were deceased, should be diagnosed by means of documented clinical evidence of periodontal disease or from reported case histories. Few studies have documented the association of LAP with other hereditary disorders such as Turners syndrome, and dentinogenesis imperfecta.[26],[30] Further studies should be carried out to understand association if any between the inheritance of LAP and other hereditary diseases such as thalassemia, hemophilia, and Marfan's syndrome.


  Conclusions Top


Even though inheritance pattern from our systematic review, based on a total of 294 families with approximately 1680 members at risk of LAP apparently shows an autosomal recessive mode of inheritance, the data are meager to conclude that localized aggressive periodontitis is solely inherited through autosomal recessive mode as there are various other factors playing a hand in the occurrence of the disease. Hence, it would not be erroneous to say that our results are largely inconclusive/may be LAP is multifactorial.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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